Malaria is the most significant vector-borne disease and annually it accounts for over two million deaths in people worldwide. The long-term objective of this research is to develop strains of vector mosquitoes that are genetically refractory to the transmission of malaria parasites. These insects will be used to test the hypothesis that an increase in the frequency of a gene or allele that confers decreased vector competence to a population of mosquitoes will lead to a reduction in the incidence and prevalence of malaria. Following successful studies using Aedes aegypti and Plasmodium gallinaceum as a malaria model system, the work proposed here addresses a major vector of human malaria, Anopheles gambiae. We will isolate and characterize genes expressed specifically in the adult female fat body cells of An. gambiae and use transgenesis to identify active promoters from the genes that will be used to express an anti-parasite effector molecule. The specific aims of this proposal are to: 1) isolate and characterize cDNA clones corresponding to genes expressed in the fat body cells of adult female An. gambiae; 2) isolate and characterize genomic clones for promoters that drive the expression of genes in the adult female fat body cells of An. gambiae; and 3) establish germ-line transformed strains of An. stephensi and An. gambiae expressing reporter genes under the control of promoters derived from genes expressed specifically in the adult female fat body cells.